Loading presentation...

Present Remotely

Send the link below via email or IM

Copy

Present to your audience

Start remote presentation

  • Invited audience members will follow you as you navigate and present
  • People invited to a presentation do not need a Prezi account
  • This link expires 10 minutes after you close the presentation
  • A maximum of 30 users can follow your presentation
  • Learn more about this feature in our knowledge base article

Do you really want to delete this prezi?

Neither you, nor the coeditors you shared it with will be able to recover it again.

DeleteCancel

Make your likes visible on Facebook?

Connect your Facebook account to Prezi and let your likes appear on your timeline.
You can change this under Settings & Account at any time.

No, thanks

Haematological Malignancy

No description
by

Jordan Tsigarides

on 7 November 2016

Comments (0)

Please log in to add your comment.

Report abuse

Transcript of Haematological Malignancy

Same as ALL except...

Immunophenotyping: Differentiates AML from ALL
HELPPPPPPPPP!


Sepsis
: Antibiotics
Bleeding
: Blood/Platelet Transfusion
Hyperuricaemia
: Allopurinol (prevent)
Leucostasis
: Leucapheresis

All The Above: Fluids!
Acute Lymphoid Leukaemia
Children Aged 2-8
Immature
Acute Myeloid Leukaemia
Haematological Malignancies
Haematopoeisis
Types
Location of Affected Cells:
Bone Marrow

Leukaemias + Myeloproliferative Disorders

Outside of the Bone Marrow

Lymphomas
Both
Myeloma
Mutations occur in undifferentiated daughter cells
Mature
Myeloproliferative Disorders
Chronic Lymphoid Leukaemia
Radiation

Chemotherapy

Viruses

Genetics
Risk Factors
Down's Syndrome
EBV + Human T-cell Leukaemia Virus
S
T
B
Maturity Stops Here
Mutations occur in more differentiated daughter cells
S
T
B
Maturity Stops Here
More Differentiated

Less Proliferative
More Differentiated

Less Proliferative
Leukaemia Vs Lymphoma
Diffusely spread out in bone marrow
Then spill into circulation
Cells
STICK TOGETHER
and form a localised mass
A small amount of cells can enter circulation
Blast cells are bigger
Less cytoplasm
Difficult to differentiate
Key Point - Acute Leukaemias
>20% Blast Cells
in
Bone Marrow or Blood Smear
Presentation
Investigations
Treatment
Cancer
Weight Loss, Malaise, Fevers, Night Sweats

Blasts In Marrow
Bone Pain

Blasts Invading
Lymphadenopathy
Splenomegaly

High Turnover
Gout!?
Tumour Lysis Synd
Low RBC
Anaemia = Fatigue, SOB & Pallor

Low WBC
Infections

Low Platelets
Easy Bruising/Petechiae
U
B
E
X
Special
Blood Cultures
- If Septic
Full Blood Count
= Pancytopaenia/Leukocytosis
Blood Smear
= >20% Blasts
Clotting
= Bad
U+Es
= Acute Kidney Damage/High K
'Acute' Leukaemia means ACUTE presentation

Commonly present critically ill with Bone Marrow Failure

Massive Haemorrhage or Sepsis
CXR

+
Abdo/Chest CT Scan
To look for Abdominal/Chest Lymphadenopathy
Bone Marrow Biopsy
= >20% Blasts
/ special
LP
=

CNS Involvement
Immunophenotyping
- Type of Leukaemia

Cytogenetics
- Type of Mutation = Prognosis
Types/Classification
It's very very unlikely you need to know this...
Morphology
French-American-British
L1: Small
L2: Big
L3: Burkitt's

Pre 2008
Immunology
B-Cell
Pre-B
B-Cell
Pro-B
Common

T-Cell
Pre-T
T-Cell

1. Non-Pharmacological
Support/Education

2. Pharmacological
Treat Complications
Chemotherapy - Induce Remission
Radiotherapy - Total Body

3. Surgical/Special
Stem Cell/Bone Marrow Transplantation - Young/Fit

Pretty much the same as ALL with a few differences...
Adults:
Increases with age
Presentation
Gum Hypertrophy - Specific for AML
Investigations
Types/Classification
Treatment
Auer Rods
M0-M7
+
Loads of Subtypes...
Do you remember the structure?

1. Non-pharmacological
2. Pharmacological
3. Surgical/Special
Management influenced by subtype
Curable but Aggressive
Rarely Invade Other Organs (Except Gums/CNS) = Rarely cause Lymphadenopathy/Splenomegaly
ALL the kids respond to treatment
Elderly
Presentation/Progression
Asymptomatic
Over time mature leukaemic cells overwhelm bone marrow and spill out into the circulation
Cancer: Weight loss, Malaise, Fever & Night Sweats
Abundance of Mature Leukaemic Cells:
Lymphadenopathy
Splenomegaly
Increased Infection Risk (hypogammaglobulinaemia)
Bone Marrow Failure (anaemia & bleeding)
Transformation into Diffuse Large B-Cell Lymphoma
Commonest Leukaemia in Western Adults
Initial Investigations
First Changes (FBC)
:
High White Cell Count
High Lymphocytes (usually >20)

Then with Blood Smear
:
Smear Cell
Where the mature but fragile leukaemic cells break open when put on a slide

Neutropenia
Lymphocytosis (Mature)
Later Investigations
Bone Marrow Biopsy:
Infiltration of Lymphocytes (>30%)

Immunophenotyping:
Confirms the diagnosis + Differentiates from other Lymphocytoses

Cytogenetics:
Prognosis

Immunoglobulins: Hypogammaglobulinaemia
Bloods: Anaemia, Thrombocytopaenia + Deranged Clotting -
Advanced Disease
Side Point: What's the Difference Between
Leukaemoid Reaction
Reactive Leukocytosis
Leukaemia
1.
"Watchful Waiting"


2.
Supportive
Treat complications

3.
"Curative"
Chemotherapy
Monoclonal Antibodies (Rituximab)
Stem Cell Transplantation (young/fit)


Treatment
Mnemonic - B Disease
B Lymphocytes (95%)
B one Marrow Failure
B leeding
B roken Cells (Smear Cells)
Chronic Myeloid Leukaemia
Essential Thrombocythaemia
Myelofibrosis
Polycythaemia Rubra Vera
Chronic Leukaemia of Granulocytes
Middle Aged
Acceleration Stage
"Blast" Stage
Chronic Stage (3-6yrs)
Commonly
Asymptomatic
Raised WCC
- predominantly granulocytes

85% of Initial Presentations

Massive Splenomegaly
can occur as WBCs get trapped in the Spleen
Cancer Symptoms
: Fatigue, Weight Loss, Fever + Night Sweats

"Leukoerythroblastic"

Blood Smear
- Difficult to differentiate from Leukaemoid reaction + Myelofibrosis
"Cruising Stage" - Increased production of granulocytes in the marrow
Anaemia:
Pallor, Fatigue, SOB

10-19% Blasts on Blood Smear


Production of Blast cells = Filling up Bone Marrow = Spilling over into circulation
Transformation into Acute Leukaemia as Blasts Saturate the Bone Marrow
Bone Pain
Gout
Acute Kidney Injury

>20% Blasts on Blood Smear


Nearly all CML patients are:

PHILADELPHIA CHROMOSOME
positive
Top CML Point
Philadelphia Cheese Makes Lunch
Treatment
Imatinib
- Tyrosine Kinase Inhibitor = Stops the faulty gene from working

Stem Cell Transplant
Young and Fit
Refractory to Imatinib
Only 'curative' treatment
Key Points/Definitions
Myeloid

=
The cell line responsible for production of granulocytes, platelets, RBCs & Mast Cells

Lymphoid =

The cell line responsible for production of Natural Killer Cells & Lymphocytes (B & T) plus Plasma Cells (from B cells)

AML = Acute Myeloid Leukaemia =
Characterised by >20% blast cells on blood smear/marrow - presenting with bone marrow failure in adults -
AUER RODS

ALL = Acute Lymphoid Leukaemia =

Characterised by >20% blast cells on blood smear/marrow - presenting with bone marrow failure in children

CLL = Chronic Lymphoid Leukaemia =

Characterised by increased WBCs (lymphocytes), usually presenting asymptomatically in the elderly - Can transform into Lymphoma -
SMEAR CELLS

Myeloproliferative Disorder =

A group of 4 conditions affecting the Myeloid line leading to overproduction of one particular cell - CML, Myelofibrosis, Essential Thrombocythaemia + Polycythaemia Rubra Vera

CML =

A type of myeloproliferative disorder - Characterised by increased WBCs (granulocytes) + Massive Splenomegaly with 3 distinct stages in the middle aged - Transforms into Acute Leukaemia eventually -
PHILADELPHIA CHROMOSOME

Myelofibrosis =

A type of myeloproliferative disorder -

Characterised by increased Megakaryocytes leading to production of factors that promote fibrosis of the bone marrow - Presents similarly to CML with massive splenomegaly - Bone Marrow Trephine biopsy to diagnose -
TEAR DROP POIKILOCYTES (blood smear)

Mnemonics
ALL =
ALL Kids Respond to Treatment
(ALL affects kids and has a good prognosis)

CLL=

B-Disease:
B
-Lymphocytes (95%)
B
one Marrow Failure
B
leeding
B
roken Cells (Smear Cells)

Causes of Splenomegaly =
5 Hs:
H
ypertension (Portal Hypertension)
H
aematological Malignancy (All discussed)
H
IV (+ EBV + Malaria)
H
eart Failure
H
aemolysis

Causes of Massive Splenomegaly =
Massive:
c
M
l
M
yelofibrosis
M
alaria

Essential Thrombocythaemia =
A type of myeloproliferative disorder - Characterised by increased platelets leading to increased risk of thrombosis and bleeding - Diagnosis of exclusion

Polycythaemia Rubra Vera =

A type of myeloproliferative disorder - Characterised by increased red blood cells leading to increased blood viscosity and clotting risk - Presents with 'vascular phenomenon' symptoms such as headache and visual disturbance as well as facial plethora -
JAK2 MUTATION

Its all about this fella...
Megakaryocyte
What Happens?
Lots of abnormal

Megakaryocytes
Instead of making Platelets they produce fibroblasts that stimulate fibrosis
Bone Marrow Fibrosis
occurs

Presentation:
Systemic Features - Weight loss, fatigue, fever, night sweats
Bone Marrow Failure - Anaemia, bleeding, infections
MASSIVE Splenomegaly
Specifics to Remember
Blood Smear:


Bone Marrow Tap =

Dry
Bone Marrow Trephine

Essential for Diagnosis

Can develop from PRV or ET
Can evolve into AML
Leucoerythroblastic Picture with Tear Drop Poikilocytes
Treatment Options
Non-pharmacological:
Support
Pharmacological:
JAK2 Inhibitor (Ruxilotinib)

+ Treat Bone Marrow Failure
Surgical/Special:

Stem Cell Transplant

(only curative option)

Prognosis is Poor = 5 years after diagnosis
Fortunately it is
very rare
WHat Happens?
Megakaryocytes Proliferate leading to

Increased Abnormal Platelets

Increased Platelets
=

Clotting
= Headaches, Dizziness, Erythromelalgia (painful red extremities)
Decreased Quality of Platelets =

Bleeding

= Easy

Bruising
Signs:
Splenomegaly
It's Difficult to Pin Down...
The Point Is...
Diagnosis of Exclusion:
Prolonged raised platelet count
All other causes ruled out

(there's a lot)
Treatment (when you finally find Wally):
Hydroxyurea
(to bring platelet count down)
Aspirin
(to inhibit the rubbish platelets)
Proliferation of Multiple Myeloid Cell Lineages
RBCs, Platelets, Mast Cells & Neutrophils
Caused by
JAK2 Mutation
Presentation
Increase in:

RBCs

Thick Blood
Clotting
Headaches
Visual Disturbance
Erythromelalgia
MI/PE/Stroke/Gangrene
Increased Turnover
+ Greater Number
Gout + Facial Plethora
Mast Cells
Increased Histamine Release
Pruritis
How to Diagnose It...
As with all patients:
/ Urine
Renal problems can cause increased RBCs/Hb due to EPO
FBC:
Raised RBCs, Hb, Hct, PLTs & Neutrophils
U+Es:
Renal problems
LFTs:
Liver problems

Chest X-ray:
Lung Problems (2nd Polycythaemia)

Abdo USS:
Look for other causes + Splenomegaly

Elderly Patients
Bone Marrow Biopsy:
Lots of cells (hypercellularity) + Abnormal Megakaryocytes

Cytogenetics:

Not routine but can show abnormalities

/ Special
How to Treat It...
Keep Haematocrit < 0.45
Venesection
(Blood Letting)

Low Dose Aspirin

Cytoreductive Therapy
Dr Jordan Tsigarides (UEA)
Hydroxyurea
Interferon
rine
loods
CG
ray
(Richter's Transformation)
50% = JAK2
Well... 80%
Full transcript